Xerostomia due to systemic disease: a review of 20 conditions and mechanisms

H Mortazavi, M Baharvand, A Movahhedian, M Mohammadi, A Khodadoustan, H Mortazavi, M Baharvand, A Movahhedian, M Mohammadi, A Khodadoustan

Abstract

Xerostomia is a common complaint of nearly half of the elderly population and about one-fifth of younger adults. It causes several signs and symptoms, and compromise oral functions and health-related quality-of-life. Multiple reasons are proposed to describe the etiology of xerostomia such as local factors, psychogenic factors, and systemic diseases. In order to manage xerostomia effectively, identification of the main causality is mandatory. The aim of this review was to present systemic diseases leading to xerostomia with their mechanisms of action. We used various general search engines and specialized databases such as Google, Google Scholar, Yahoo, PubMed, PubMed Central, MedLine Plus, Medknow, EBSCO, ScienceDirect, Scopus, WebMD, EMBASE, and authorized textbooks to find relevant topics by means of Medical Subject Headings keywords such as "xerostomia," "hyposalivations," "mouth dryness," "disease," and "systemic." We appraised 97 English-language articles published over the last 40 years in both medical and dental journals including reviews, meta-analysis, original papers, and case reports. Upon compilation of relevant data, it was concluded that autoimmune diseases most frequently involve salivary glands and cause xerostomia followed by diabetes mellitus, renal failure, and graft-versus-host disease. Moreover, the underlying mechanisms of systemic disease-related xerostomia are: autoimmunity, infiltration of immunocompetent cells, granuloma formation, fibrosis and dehydration, deposition of proteinaceous substances, bacterial infection, and side-effects of medications.

Keywords: Disease; Hyposalivations; Mouth dryness; Systemic; Xerostomia.

Conflict of interest statement

Conflict of Interest: None declared.

References

    1. Thomson WM, Chalmers JM, Spencer AJ, Williams SM. The Xerostomia Inventory: A multi-item approach to measuring dry mouth. Community dent health. 1999;16:12–7.
    1. Thomson WM. Issues in the epidemiological investigation of dry mouth. Gerodontology. 2005;22:65–76.
    1. Murray Thomson W, Poulton R, Mark Broadbent J, Al-Kubaisy S. Xerostomia and medications among 32-year-olds. Acta Odontol Scand. 2006;64:249–54.
    1. Guggenheimer J, Moore PA. Xerostomia etiology, recognition and treatment. JADA. 2003;134:61–9.
    1. Fox PC. Xerostomia: Recognition and management. Dent Assist. 2008;77:44–8.
    1. Grötz K, Genitsariotis S, Vehling D, Al-Nawas B. Long-term oral Candida colonization, mucositis and salivary function after head and neck radiotherapy. Support Care Cancer. 2003;11:717–21.
    1. Momm F, Volegova-Neher NJ, Schulte-Mönting J, Guttenberger R. Different saliva substitutes for treatment of xerostomia following radiotherapy. Strahlenther Onkol. 2005;181:231–6.
    1. Turner M, Jahangiri L, Ship JA. Hyposalivation, xerostomia and the complete denture. A systematic review. JADA. 2008;139:146–50.
    1. Daniels TE. Evaluation, differential diagnosis, and treatment of xerostomia. J Rheumatol Suppl. 2000;61:6.
    1. Rayman S, Dincer E, Almas K. Xerostomia: Diagnosis and management in dental practice. N Y State Dent J. 2010;76:24–7.
    1. Vasconcelos ACU, Soares MSM, Almeida PC, Soares TC. Comparative study of the concentration of salivary and blood glucose in type 2 diabetic patients. J Oral Sci. 2010;52:293–8.
    1. Bakianian Vaziri P, Vahedi M, Mortazavi H, Abdollahzadeh Sh, Hajilooi M. Evaluation of salivary glucose, IgA and flow rate in diabetic patients: A case-control study. J Dent (Tehran) 2010;7:13–8.
    1. Olokoba AB, Obateru OA, Olokoba LB. Type 2 diabetes mellitus: a review of current trends. Oman Med J. 2012;27:269.
    1. Casqueiro J, Casqueiro J, Alves C. Infections in patients with diabetes mellitus: A review of pathogenesis. Indian J Endocrinol Metab. 2012;16:S27.
    1. Bajaj S, Prasad S, Gupta A, Singh VB. Oral manifestations in type-2 diabetes and related complications. Indian J Endocrinol Metab. 2012;16:777–9.
    1. Khovidhunkit S-oP, Suwantuntula T, Thaweboon S, Mitrirattanakul S, Chomkhakhai U, Khovidhunkit W. Xerostomia, hyposalivation, and oral microbiota in type 2 diabetic patients: A preliminary study. J Med Assoc Thai. 2009;92:1220–8.
    1. Busato IMS, Ignácio SA, Brancher JA, Grégio AMT, Machado MÂN, Azevedo-Alanis LR. Impact of xerostomia on the quality of life of adolescents with type 1 diabetes mellitus. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;108:376–82.
    1. Costa CC, Resende GB, Souza JM, Tavares SS, Almeida IC. Study of the oral manifestations in diabetic children and their correlation variables. Arq Bras Endocrinol Metabol. 2004;48:374–8.
    1. Cooper JD, Simmonds MJ, Walker NM, Burren O, Brand OJ, Guo H, et al. Seven newly identified loci for autoimmune thyroid disease. Hum Mol Genet. 2012;21:5202–8.
    1. Hutfless S, Matos P, Talor MV, Caturegli P, Rose NR. Significance of prediagnostic thyroid antibodies in women with autoimmune thyroid disease. J Clin Endocrinol Metab. 2011;96:E1466–71.
    1. Cárdenas Roldán J, Amaya-Amaya J, Castellanos-de la Hoz J, Giraldo-Villamil J, Montoya-Ortiz G, Cruz-Tapias P, et al. Autoimmune thyroid disease in rheumatoid arthritis: A global perspective. Arthritis 2012. 2012:864907.
    1. Karsh J, Pavlidis N, Weintraub BD, Moutsopoulos HM. Thyroid disease in Sjögren's syndrome. Arthritis Rheum. 1980;23:1326–9.
    1. D’Arbonneau F1, Ansart S, Le Berre R, Dueymes M, Youinou P, Pennec YL. Thyroid dysfunction in primary Sjögren's syndrome: A long-term followup study. Arthritis Rheum. 2003;49:804–9.
    1. Okoje V, Obiechina A, Aken’Ova Y. Orofacial lesions in 126 newly diagnosed HIV/AIDS patients seen at the University College Hospital, Ibadan. Afr J Med Med Sci. 2006;35:97–101.
    1. Nokta M. Oral manifestations associated with HIV infection. Curr HIV/AIDS Rep. 2008;5:5–12.
    1. Reznik D. Oral manifestations of HIV disease. Top HIV Med. 2005;13:143–8.
    1. Expósito-Delgado A, Vallejo-Bolaños E, Martos-Cobo E. Oral manifestations of HIV infection in infants: A review article. Med Oral Patol Oral Cir Bucal. 2004;9:415.
    1. Pinto A, De Rossi SS. Salivary gland disease in pediatric HIV patients: an update. J Dent Child (Chic) 2004;71:33–7.
    1. Sharma G, Pai K, Suhas S, Ramapuram J, Doshi D, Anup N. Oral manifestations in HIV/AIDS infected patients from India. Oral Dis. 2006;12:537–42.
    1. Taiwo O, Okeke E, Jalo P, Danfillo I. Oral manifestation of HIV/AIDS in Plateau state indigenes, Nigeria. West Afr J Med. 2006;25:32–7.
    1. Freed JR, Marcus M, Freed BA, Der-Martirosian C, Maida CA, YOUNAI FS, et al. Oral health findings for HIV-infected adult medical patients from the HIV Cost and Services Utilization Study. JADA. 2005;136:1396–405.
    1. Sontakke SA, Umarji H, Karjodkar F. Comparison of oral manifestations with CD4 count in HIV-infected patients. Indian J Dent Res. 2011;22:732.
    1. Pinheiro A, Marcenes W, Zakrzewska J, Robinson P. Dental and oral lesions in HIV infected patients: a study in Brazil. Int Dent J. 2004;54:131–7.
    1. Nittayananta W, Chanowanna N, Jealae S, Nauntofte B, Stoltze K. Hyposalivation, xerostomia and oral health status of HIV-infected subjects in Thailand before HAART era. J Oral Pathol Med. 2010;39:28–34.
    1. Lin A, Johnson D, Stephan K, Yeh C-K. Alteration in salivary function in early HIV infection. J Dent Res. 2003;82:719–24.
    1. Ramos-Casals M, Trejo O, García-Carrasco M, Font J. Therapeutic management of extrahepatic manifestations in patients with chronic hepatitis C virus infection. Rheumatology (Oxford) 2003;42:818–28.
    1. Prunoiu C, Georgescu EF, Georgescu M, Simionescu C. Sjogren's syndrome associated with chronic hepatitis C-the benefit of the antiviral treatment. Rom J Morphol Embryol. 2008;49:557–62.
    1. Grossmann SdMC, Teixeira R, de Oliveira GC, Gleber-Netto FO, Araújo FMG, Araújo FM, et al. Xerostomia, hyposalivation and sialadenitis in patients with chronic hepatitis C are not associated with the detection of HCV RNA in saliva or salivary glands. J Clin Pathol. 2010;63:1002–7.
    1. de Mattos Camargo Grossmann S, Teixeira R, de Oliveira GC, do Carmo MAV. Detection of HCV RNA in saliva does not correlate with salivary flow or xerostomia in patients with chronic hepatitis C. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;109:851–6.
    1. Carrozzo M, Gandolfo S. Oral diseases possibly associated with hepatitis C virus. Crit Rev Oral Biol Med. 2003;14:115–27.
    1. Nawito Z, Amin A, El-Fadl SA, El Einen KA. Sicca complex among Egyptian patients with chronic hepatitis C virus infection. Clin Rheumatol. 2011;30:1299–304.
    1. Giordano N, Amendola A, Papakostas P, Cipolli F, Agate VM, Battisti E, et al. Immune and autoimmune disorders in HCV chronic liver disease: Personal experience and commentary on literature. New Microbiol. 2005;28:311–7.
    1. Nagao Y, Hashimoto K, Sata M. Candidiasis and other oral mucosal lesions during and after interferon therapy for HCV-related chronic liver diseases. BMC Gastroenterol. 2012;12:155.
    1. Aghemo A, Rumi MG, Monico S, Banderali M, Russo A, Ottaviani F, et al. Ribavirin impairs salivary gland function during combination treatment with pegylated interferon alfa-2a in hepatitis C patients. Hepat Mon. 2011;11:918–24.
    1. Arvey A, Tempera I, Lieberman PM. Interpreting the Epstein-Barr Virus [EBV] Epigenome Using High-Throughput Data. Viruses. 2013;5:1042–54.
    1. Hallee TJ, Evans AS, Niederman JC, Brooks CM, Voegtly JH. Infectious mononucleosis at the United States Military Academy. A prospective study of a single class over four years. Yale J Biol Med. 1974;47:182–95.
    1. Lossius A, Johansen JN, Torkildsen Ø, Vartdal F, Holmøy T. Epstein-Barr Virus in Systemic Lupus Erythematosus, Rheumatoid Arthritis and Multiple Sclerosis—Association and Causation. Viruses. 2012;4:3701–30.
    1. Fox R, Chilton T, Scott S, Benton L, Howell F, Vaughan J. Potential role of Epstein-Barr virus in Sjögren's syndrome. Rheum Dis Clin North Am. 1987;13:275–92.
    1. Stadler LP, Bernstein DI, Callahan ST, Ferreira J, Simone GAG, Edwards KM, et al. Seroprevalence of cytomegalovirus [CMV] and risk factors for infection in adolescent males. Clin Infect Dis. 2010;51:e76–81.
    1. Burns J. Persistent Cytomegalovirus infection-The etiology of Sjogren's Syndrome. Med Hypotheses. 1983;10:451–60.
    1. Scully C. Sjögren's syndrome: no demonstrable association by serology of secondary Sjögren's syndrome with cytomegalovirus. J Oral Pathol Med. 1990;19:43–4.
    1. Poetker SK, Porto AF, Giozza SP, Muniz AL, Caskey MF, Carvalho EM, et al. Clinical manifestations in individuals with recent diagnosis of HTLV type I infection. J Clin Virol. 2011;51:54–8.
    1. Proietti FA, Carneiro-Proietti ABF, Catalan-Soares BC, Murphy EL. Global epidemiology of HTLV-I infection and associated diseases. Oncogene. 2005;24:6058–68.
    1. Manns MP, Rambusch EG. Autoimmunity and extrahepatic manifestations in hepatitis C virus infection. J Hepatol. 1999;31(Suppl 1):39–42.
    1. Obermayer-Straub P, Manns MP. Hepatitis C and D, retroviruses and autoimmune manifestations. J Autoimmun. 2001;16:275–85.
    1. Lee SJ, Lee JS, Shin MG, Tanaka Y, Park DJ, Kim TJ, et al. Detection of HTLV-1 in the labial salivary glands of patients with Sjogren's syndrome: A distinct clinical subgroup? J Rheumatol. 2012;39:809–15.
    1. Hida A, Kawabe Y, Kawakami A, Migita K, Tominaga M, Nakamura H, et al. HTLV-I associated Sjögren's syndrome is aetiologically distinct from anti-centromere antibodies positive Sjögren's syndrome. Ann Rheum Dis. 1999;58:320–2.
    1. Ohyama Y, Nakamura S, Hara H, Shinohara M, Sasaki M, Ikebe-Hiroki A, et al. Accumulation of human T lymphotropic virus type I-infected T cells in the salivary glands of patients with human T lymphotropic virus type I-associated Sjogren's syndrome Arthritis Rheum. 1998;41:1972–8.
    1. Neville BW, Damm DD, Allen CM, Bouqout JE. St Louis: Saunders Elsevier; 2009. Oral and maxillofacial pathology; p. 203.
    1. Mamais C, Dias A, Walker J, Vydianath SR. Parotid actinomycosis mimicking metastatic lymphadenopathy. West Indian Med J. 2011;60:349–50.
    1. Sittitrai P, Srivanitchapoom C, Pattarasakulchai T, Lekawanavijit S. Actinomycosis presenting as a parotid tumor. Auris Nasus Laryn×. 2012;39:241–3.
    1. Zalewska A, Knaś M, Waszkiewicz N, Waszkiel D, Sierakowski S, Zwierz K. Rheumatoid arthritis patients with xerostomia have reduced production of key salivary constituents. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013;115:483–90.
    1. Anurag Gupta B, Epstein JB, Sroussi H. Hyposalivation in elderly patients. J Can Dent Assoc. 2006;72:841–6.
    1. Jensen J, Bergem H, Gilboe IM, Husby G, Axell T. Oral and ocular sicca symptoms and findings are prevalent in systemic lupus erythematosus. J Oral Pathol Med. 1999;28:317–22.
    1. Anurag Gupta B, Epstein JB, Sroussi H. Hyposalivation in elderly patients. J Can Dent Assoc. 2006;72:841–6.
    1. Karp JK, Akpek EK, Anders RA. Autoimmune hepatitis in patients with primary Sjögren's syndrome: A series of two-hundred and two patients. Int J Clin Exp Pathol. 2010;25(3):582–6.
    1. Kumagi T, Heathcote EJ. Primary biliary cirrhosis. Orphanet J Rare Dis. 2008;23(3):1.
    1. Selmi C, Meroni PL, Gershwin ME. Primary biliary cirrhosis and Sjögren's syndrome: autoimmune epithelitis. J Autoimmun. 2012;39:34–42.
    1. Mang F-W, Michieletti P, O’Rourke K, Cauch-Dudek K, Diamant N, Bookman A, et al. Primary biliary cirrhosis, sicca complex, and dysphagia. Dysphagia. 1997;12:167–70.
    1. Cazal C, Sobral APV, Neves R, Freire-Filho F, Cardoso A, da Silveira M. Oral complaints in progressive systemic sclerosis: Two cases report. Med Oral Patol Oral Cir Bucal. 2008;13:E114–8.
    1. Albilia JB, Lam DK, Blanas N, Clokie CM, Sándor GK. Small mouths… Big problems? A review of scleroderma and its oral health implications. J Can Dent Assoc. 2007;73:831–6.
    1. Janin A, Gosselin B, Gosset D, Hatron P, Sauvezie B. Histological criteria of Sjögren's syndrome in scleroderma. Clin Exp Rheumatol. 1989;7:167.
    1. Sekhri V, Sanal S, DeLorenzo LJ, Aronow WS, Maguire GP. Cardiac sarcoidosis: A comprehensive review. Arch Med Sci. 2011;7:546–54.
    1. Mansour M, Al-Hashimi I, Wright J. Coexistence of Sjögren's syndrome and sarcoidosis: A report of five cases. J Oral Pathol Med. 2007;36:337–41.
    1. Surattanont F, Mandel L, Wolinsky B. Bilateral parotid swelling caused by sarcoidosis. JADA. 2002;133:738–41.
    1. Poate T, Sharma R, Moutasim KA, Escudier M, Warnakulasuriya S. Orofacial presentations of sarcoidosis: A case series and review of the literature. Br Dent J. 2008;205:437–42.
    1. Babazade F, Mortazavi H, Jalalian H. Parotid tuberculosis: A forgotten suspicion (a case report and literature review) Int J Dermatol. 2012;51:588–91.
    1. Greenberg MS, Glick M, Ship JA. Ontario: BC Decker Inc; 2008. Burket's Oral Medicine; pp. 213–14.
    1. Klopfleisch R, Olias P. The Pathology of comparative animal models of human haemochromatosis. J Comp Pathol. 2012;147:460–78.
    1. Sánchez-Pablo M-A, González-García V, del Castillo-Rueda A. Study of total stimulated saliva flow and hyperpigmentation in the oral mucosa of patients diagnosed with hereditary hemochromatosis. Series of 25 cases. Med Oral Patol Oral Cir Bucal. 2012;1(17):e45–9.
    1. Wey SJ, Chen YM, Lai PJ, Chen DY. Primary sjögren syndrome manifested as localized cutaneous nodular amyloidosis. J Clin Rheumatol. 2011;17:368–70.
    1. Elfatoiki FZ, Funck Brentano E, Blanc F, Clerici T, Saiag P. Nodular cutaneous amyloidosis associated with Sjögren's syndrome. Ann Dermatol Venereol. 2013;140:378–81.
    1. Juusela P, Tanskanen M, Nieminen A, Kari K, Suominen L, Uitto VJ, Kiuru-Enari S. Xerostomia in hereditary gelsolin amyloidosis. Amyloid. 2013;20:39–44.
    1. Sowa T, Komatsu T, Fujinaga T, Kato T. A case of solitary pulmonary nodular amyloidosis with Sjögren's syndrome. Ann Thorac Cardiovasc Surg. 2013;19:247–9.
    1. M SP, Rajan PM, Santhi S, Jothimalar Blood Lead in End-Stage Renal Disease Patients who were on Maintainence Haemodialysis. J Clin Diagn Res. 2012;6:1633–5.
    1. Postorino M, Catalano C, Martorano C, Cutrupi S, Marino C, Cozzupoli P, et al. Salivary and lacrimal secretion is reduced in patients with ESRD. Am J Kidney Dis. 2003;42:722–8.
    1. Dirschnabel AJ, Martins AS, Dantas S, Ribas MO, Grégio A, Alanis L, et al. Clinical oral findings in dialysis and kidney-transplant patients. Quintessence Int. 2011;42:127–33.
    1. Lexner MO, Bardow A, Hertz JM, Almer L, Nauntofte B, Kreiborg S. Whole saliva in X-linked hypohidrotic ectodermal dysplasia. Int J Paediatr Dent. 2007;17:155–62.
    1. Präger TM, Finke C, Miethke R-R. Dental findings in patients with ectodermal dysplasia. J Orofac Orthop. 2006;67:347–55.
    1. Nordgarden H, Jensen J, Storhaug K. Oligodontia is associated with extra-oral ectodermal symptoms and low whole salivary flow rates. Oral Dis. 2001;7:226–32.
    1. Noce C, Gomes A, Copello A, Barbosa R, Sant’anna S, Moreira M, et al. Oral involvement of chronic graft-versus-host disease in hematopoietic stem cell transplant recipients. Gen Dent. 2011;59:458–62. quiz 463-4.
    1. Nagler RM, Nagler A. Salivary gland involvement in graft-versus-host disease: The underlying mechanism and implicated treatment. Isr Med Assoc J. 2004;6:167–72.
    1. Hull K, Kerridge I, Schifter M. Long-term oral complications of allogeneic haematopoietic SCT. Bone Marrow Transplant. 2012;47:265–70.
    1. Boer C, Correa M, Miranda E, de Souza C. Taste disorders and oral evaluation in patients undergoing allogeneic hematopoietic SCT. Bone Marrow Transplant. 2010;45:705–11.
    1. de la Rosa-Garcia E, Bologna-Molina R, Vega-González M, de Jesus T. Graft-versus-host disease, an eight case report and literature review. Med Oral Patol Oral Cir Bucal. 2006;11:E486–92.
    1. Proulx M, De Courval FP, Wiseman MA, Panisset M. Salivary production in Parkinson's disease. Mov Disord. 2005;20:204–7.
    1. Cersósimo M, Tumilasci O, Raina G, Benarroch E, Cardoso E, Micheli F, et al. Hyposialorrhea as an early manifestation of Parkinson disease. Auton Neurosci. 2009;150:150–1.

Source: PubMed

3
Prenumerera